视网膜母细胞瘤免疫治疗研究进展

视网膜母细胞瘤（RB）作为一种儿童最常见的恶性肿瘤，其治疗方式一直备受关注。目前，虽然RB已成功采用一系列保守治疗方式来保留眼球和保存视功能，但由于RB可通过视神经扩散到中枢神经系统，并通过巩膜、眶骨的淋巴和血液循环进行远处转移。在这种情况下，RB的多数治疗方式的治疗效果均不佳。目前需要一种新的RB治疗方式，不仅能够更有效地抑制肿瘤生长，同时也能控制肿瘤的远处转移。免疫治疗能使正常组织的损伤最小化，更具有特异性，且可以防止随后的肿瘤复发，对于治疗RB具有很大的应用前景。本文将对RB免疫治疗最新进展进行综述。     

Regulation of epigenetic homeostasis in uveal melanoma and retinoblastoma

Uveal melanoma (UM) and retinoblastoma (RB), which cause blindness and even death, are the most frequently observed primary intraocular malignancies in adults and children, respectively. Epigenetic studies have shown that changes in the epigenome contribute to the rapid progression of both UM and RB following classic genetic changes. The loss of epigenetic homeostasis plays an important role in oncogenesis by disrupting the normal patterns of gene expression. The targetable nature of epigenetic modifications provides a unique opportunity to optimize treatment paradigms and establish new therapeutic options for both UM and RB with these aberrant epigenetic modifications. We aimed to review the research findings regarding relevant epigenetic changes in UM and RB. Herein, we 1) summarize the literature, with an emphasis on epigenetic alterations, including DNA methylation, histone modifications, RNA modifications, noncoding RNAs and an abnormal chromosomal architecture; 2) elaborate on the regulatory role of epigenetic modifications in biological processes during tumorigenesis; and 3) propose promising therapeutic candidates for epigenetic targets and update the list of epigenetic drugs for the treatment of UM and RB. In summary, we endeavour to depict the epigenetic landscape of primary intraocular malignancy tumorigenesis and provide potential epigenetic targets in the treatment of these tumours.     

视网膜母细胞瘤诊断和治疗的研究进展

视网膜母细胞瘤(RB)是儿童最常见的眼内恶性肿瘤,常严重影响患儿的视功能、生活质量甚至生命安全。随着医学技术的不断发展,RB的诊断与治疗取得许多新的突破,有效地提高了RB患儿的保眼率及生存率。除了传统的影像学、眼科特检等检查外,基因诊断近些年来在临床上广泛开展。本文将重点对RB的诊断及治疗的新进展进行综述。     

视网膜母细胞瘤化疗耐药的研究进展

视网膜母细胞瘤(retinoblastoma，RB)是儿童最常见的眼内恶性肿瘤，化疗是目前治疗RB最常用的方法，包括静脉化疗、动脉化疗和玻璃体腔化疗。然而，RB的化疗耐药时有发生，是导致RB患者保眼治疗失败的主要原因。因此，探索RB化疗耐药的发生发展机制、寻找RB治疗新策略及药物联合治疗的新方法具有重要临床意义。本文综述了RB细胞可通过ATP结合盒式蛋白(ABC转运蛋白)、非编码RNA、表观遗传学修饰、自噬、上皮-间充质转化、细胞外基质改变等多种途径获得化疗耐药性，并对其潜在的治疗靶点或药物进行总结，以期为RB化疗耐药性的进一步研究提供参考。     

Retinoblastoma: Recent trends A mini review based on published literature

Retinoblastoma (RB) is the most common intraocular malignancy in children. Recently, there have been significant advances made in the molecular pathology and the management of the disease. Last decade has witnessed better understanding of the genetics of RB, the discovery of new tumor markers expressed by the RB tumors, the identification of high-risk histopathological factors following enucleation, and newer methods of treatment including periocular chemotherapy and superselective intraarterial chemotherapy. All these advances have translated in improved survival rates for the affected children, improved rates of eye salvage, and improved visual outcomes. This article briefly reviews these advances.Method of Literature Search: Literature on the Medline database was searched using the PubMed interface. The search strategy included MeSH and natural language terms using the keywords mentioned. Reference lists in retrieved articles and textbooks were also searched for relevant references.     

抗VEGF治疗在眼科的临床意义及研究进展

目前许多抗血管内皮生长因子(VEGF)药物被用于治疗各种眼科疾病,尤其在血管增生性眼病的治疗中扮演着重要角色,这些药物能够明显抑制新生血管且减轻水肿提高患者视力,但其长期治疗效果需要更长远的随访和研究。本文就抗VEGF在眼科的应用及研究进展进行综述,为临床应用和深入研究提供参考。     

重视对视网膜母细胞瘤患儿的个体化综合治疗

视网膜母细胞瘤（RB）是发生于婴幼儿时期最为常见的眼内恶性肿瘤。随着新治疗方法的不断出现,传统的RB治疗目标和治疗模式已逐步转变为以保留眼球和视功能作为前提的个体化综合治疗新模式。与国外发达国家相比,我国在RB的临床治疗新思路和个体化综合治疗新手段等方面尚有较大差距。目前,多数医院仍首选眼球摘除术,同时以外部放射治疗作为补充,其治疗模式相对滞后、局限和单一。因此,国内临床眼科医师应重视结合我国RB的实际发病情况,改变以往的传统治疗理念,合理借鉴国外的先进治疗经验,积极探索并逐步建立起切实可行的RB个体化综合治疗新模式。（中华职科杂志,2007,43：481-483）     

视网膜母细胞瘤治疗及研究进展

随着基础研究和临床实践的逐步深入,视网膜母细胞瘤（ RB）的治疗模式已发生改变。目前,RB的治疗方法包括局部治疗、化学治疗、放射治疗、手术治疗、基因治疗等,本文将就RB的治疗及研究进展进行综述。     

视网膜母细胞瘤综合治疗的预后及其相关因素

目的：研究视网膜母细胞瘤（RB）患儿综合治疗的预后并探讨其相关临床因素。 方法：回顾性系列病例研究。分析在深圳市眼科医院进行综合治疗的65例（92眼）RB患儿的临床资料。综合治疗的方法为以化疗为主联合局部治疗（光凝或冷冻）+眼球摘除治疗。不同结局相关临床因素的比较采用独立样本t检验,其余指标采用Fisher's精准检验。 结果：所有RB患儿的总生存率为92%,不同分期生存率差异无统计学意义。所有患儿总的保眼率为51%,E期和其他4期之问保眼率差异均有统计学意义(P<0.01)。高风险D、E期RB患儿共60例,采用化疗联合局部治疗保眼的共42例,D期18例中11例保眼成功,E期24例中4例保眼成功。治疗成功与失败患儿的初诊时间和随访时间差异无统计学意义。根据眼内肿瘤的位置将42例患儿分为3组,分析显示即周边部（包括中周部）与后极部、后极部+周边部保眼率差异有统计学意义(P=0.009、0.021)。42例患儿中4例死亡,均为肿瘤位置处于后极部的患儿,后极部与后极部+周边部2组之间病死率差异有统计学意义( P=0.045)。 结论：综合治疗提高了RB患儿的生存率,但患儿的生存率和保眼率与其临床分期及肿瘤所处的位置高度相关。     

Significance of Retinoma and Phthisis Bulbi for Retinoblastoma

Genetic counseling of retinoblastoma(RB)patients and their families is difficult and inaccurate. The data in this paper show that two ocular lesions, retinoma and phthisis bulbi, are associated with RB and can be useful in diagnosis and counseling. Phthisis bulbi is the end result of many conditions and can only be linked to RB if other evidence is present. Retinomas, on the other hand, have three distinctive clinical characteristics (irregular translucent retinal mass, calcification, and pigment epithelial disturbance) and quite accurately predict the presence of the RB gene. Recognition of the significance of retinoma and phthisis bulbi with respect to the RB gene is critical in genetic counseling. Of 34 individuals studied, 32 with retinoma and five with phthisis bulbi, two thirds had a family history of RB or RB in the other eye, and 23/37 of their offspring developed RB. The clinical course of RB in the six children known to be at risk on the basis of detection of the gene in the parent was significantly better than in 17 children that were symptomatic at the time of diagnosis.     

Retinoblastoma: Achieving new standards with methods of chemotherapy

The management of retinoblastoma (RB) has dramatically changed over the past two decades from previous radiotherapy methods to current chemotherapy strategies. RB is a remarkably chemotherapy-sensitive tumor. Chemotherapy is currently used as a first-line approach for children with this malignancy and can be delivered by intravenous, intra-arterial, periocular, and intravitreal routes. The choice of route for chemotherapy administration depends upon the tumor laterality and tumor staging. Intravenous chemotherapy (IVC) is used most often in bilateral cases, orbital RB, and as an adjuvant treatment in high-risk RB. Intra-arterial chemotherapy (IAC) is used in cases with group C or D RB and selected cases of group E tumor. Periocular chemotherapy is used as an adjunct treatment in eyes with group D and E RB and those with persistent/recurrent vitreous seeds. Intravitreal chemotherapy is reserved for eyes with persistent/recurrent vitreous seeds. In this review, we describe the various forms of chemotherapy used in the management of RB. A database search was performed on PubMed, using the terms “RB,” and “treatment,” “chemotherapy,” “systemic chemotherapy,” “IVC,” “IAC,” “periocular chemotherapy,” or “intravitreal chemotherapy.” Relevant English language articles were extracted, reviewed, and referenced appropriately.     

视网膜母细胞瘤的治疗研究进展

视网膜母细胞瘤(retinoblastoma,RB)是婴幼儿最常见的眼内恶性肿瘤,其发病与基因突变相关。为提高患儿生存率,降低眼球摘除率,治疗方法不断更新发展。目前主要治疗方法有化学治疗、放射治疗、手术治疗、物理治疗、光化学治疗、基因治疗等。本文就视网膜母细胞瘤的治疗进展进行综述。     

儿童心理行为对远视性弱视疗效的影响

目的:根据远视性弱视儿童疗效不同分组比较两组患儿行为心理差异,观察儿童心理行为对弱视疗效的影响。方法:将门诊接受弱视治疗6mo的远视性弱视儿童分为2组:(1)疗效差组:共计29例,其中男16例,女13例。(2)疗效正常对照组:共计116例,其中男64例,女52例。采用Achenbach儿童行为量表家长用表和Conners父母症状问卷对同龄的远视性弱视和对照组儿童进行评定并进行比较分析。结果:Achenbach儿童行为量表显示:疗效差组的男孩中,思维问题、注意问题和攻击性行为的评分显著高于疗效正常对照组(P<0.05);女孩中,退缩、注意问题、社交情况、社会能力总分的评分显著高于疗效正常对照组(P<0·05)。Conners父母症状问卷显示:疗效差组的男孩中,学习问题、心身问题、冲动-多动和多动指数的评分显著高于疗效正常对照组(P<0.05);女孩中,学习问题和冲动-多动的评分显著高于疗效正常对照组(P<0.05)。结论:儿童行为心理对远视性弱视治疗有明显影响,远视性弱视疗效差的患儿主要表现为多动与注意力不集中,自制能力不足,容易激发冲动造成成绩不良和学习障碍。     

A 12-year epidemiological review of retinoblastoma in Omani children

aim?To describe the epidemiology of retinoblastoma (RB) in Omani children. method?The National Cancer Registry, hospital records, and treatment abroad registers were reviewed to identify the characteristics of Omani children diagnosed with RB between 1990 and 2002. results?Twenty-nine children (12 male and 17 female) were diagnosed with RB. The age-adjusted incidence was 4.04/million/year in children <15 years and 8.33/million/year in children <5 years. The mean age at diagnosis was 32.2 months (33.8 months for unilateral RB and 13.2 months for bilateral RB). 75% had unilateral tumors and 25% had bilateral tumors. The five-year survival rate for RB was 89%. None of the patients had a family history of RB. conclusion?The incidence of RB in Oman is at par with other countries. A definite female preponderance exists in the Omani population. The proportion of unilateral RB cases is unusually high among Omani children. The five-year survival rate is almost at par with that reported in the West. Genetic studies and further longitudinal studies of surviving RB cases could further enhance the knowledge of the epidemiology of RB in Oman.     

视网膜母细胞瘤的遗传学特征及临床筛查与治疗

视网膜母细胞瘤(RB)是儿童最常见的眼内恶性肿瘤,多发于婴幼儿,可损害患儿视力、眼球,甚至危及生命。其发生和发展与基因组和表观基因组有很大关系,遗传性RB占所有病例的45%。RB的治疗和预后取决于疾病的初始阶段,当疾病被早期诊断和治疗时,存活率超过95%,当RB在晚期发生眼外播散时,存活率低于50%。因此RB的治疗重点是通过早期肿瘤的监测和预防挽救患儿生命,其次要目标是保存眼球,并最大水平地保留视力。对RB遗传学的研究有助于通过基因筛查、监测查找特异性靶点,对提高患儿的生存率、研究RB靶向治疗十分必要。     

A 12-year epidemiological review of retinoblastoma in Omani children

AIM: To describe the epidemiology of retinoblastoma (RB) in Omani children. METHOD: The National Cancer Registry, hospital records, and treatment abroad registers were reviewed to identify the characteristics of Omani children diagnosed with RB between 1990 and 2002. RESULTS: Twenty-nine children (12 male and 17 female) were diagnosed with RB. The age-adjusted incidence was 4.04/million/year in children < 15 years and 8.33/million/year in children < 5 years. The mean age at diagnosis was 32.2 months (33.8 months for unilateral RB and 13.2 months for bilateral RB). 75% had unilateral tumors and 25% had bilateral tumors. The five-year survival rate for RB was 89%. None of the patients had a family history of RB. CONCLUSION: The incidence of RB in Oman is at par with other countries. A definite female preponderance exists in the Omani population. The proportion of unilateral RB cases is unusually high among Omani children. The five-year survival rate is almost at par with that reported in the West. Genetic studies and further longitudinal studies of surviving RB cases could further enhance the knowledge of the epidemiology of RB in Oman.     

Disparities in Retinoblastoma Presentation,Treatment, and Outcomes in Developed and Less-Developed Countries

ABSTRACT

Retinoblastoma (RB) is the most common intraocular malignancy in children. In the past century, RB survival rates in developed countries (DCs) have improved from <5% to as high as 99%. In contrast, in less developed countries (LDCs) where the tumor burden is greatest, survival rates remain poor, with some countries reporting survival rates as low as 0–5%. In addition, there are disparities between DCs and LDCs in RB presentation, treatment modalities, and prognosis. These disparities are due to many underlying causes, including delays in diagnosis, access to medical care, patient and physician familiarity with the disease, availability and cost of treatment, and patient acceptance of enucleation. It is our belief that attempts to extend the improvements in prognosis achieved in DCs to various LDCs must be culturally sensitive and tailored to each country’s specific challenges, and thus, a “one-size-fits-all” approach to improving patient outcomes in LDCs is unlikely to work well. We discuss several culturally sensitive approaches that have been successfully implemented in various LDCs, including those that make use of telemedicine and “twinning” with centers of excellence around the world.     

【In Press】 Expression of multidrug resistance proteins in retinoblastoma

AIM: To elucidate the mechanism of multidrug resistance in retinoblastoma (RB), and to acquire more insights into in vivo drug resistance. METHODS: Three anticancer drug resistant Y79 human RBcells were generated against vincristine, etoposide or carboplatin, which are used for conventional chemotherapy in RB. Primary cultures from enucleated eyes after chemotherapy (PCNC) were also prepared. Their chemosensitivity to chemotherapeutic agents (vincristine, etoposide and carboplatin) were measured using MTT assay. Western blot analysis was performed to evaluate the expression of p53, Bcl-2 and various multidrug resistant proteins in RB cells. RESULTS: Following exposure to chemotherapeutic drugs, PCNC showed less sensitivity to drugs. No significant changes observed in the p53 expression, whereas Bcl-2 expression was found to be increased in the drug resistant cells as well as in PCNC. Increased expression of P-glycoprotein (P-gp) was observed in drug resistant Y79 cells; however there was no significant change in the expression of P-gp found between primary cultures of primarily enucleated eyes and PCNC. Multidrug resistance protein 1 (Mrp-1) expression was found to be elevated in the drug resistant Y79 cells as well as in PCNC. No significant change in the expression of lung resistance associated protein (Lrp) was observed in the drug resistant Y79 cells as well as in PCNC. CONCLUSION: Our results suggest that multidrug resistant proteins are intrinsically present in RB which causes treatment failure in managingRB with chemotherapy.     

纳米给药系统在眼底疾病治疗中的研究进展

眼底疾病是全球导致患者视力严重受损甚至丧失的最主要原因，由于各种生理屏障使治疗药物难以进入眼底，严重影响了眼底疾病的治疗。纳米给药系统具有纳米级尺寸、表面积/体积比值大的特点，可以负载不同理化性质的治疗药物，同时可以修饰各种表面活性物质，能够提高药物的溶解度以及生理屏障的穿透性、保护生物药物不被降解而提高药物安全性与生物利用度、并将治疗药物递送到特定的眼部靶点，具有巨大的治疗潜力。目前越来越多围绕利用纳米材料的优势治疗眼底疾病的研究已经展开并引起广泛关注，包括神经退行性病变、眼底新生血管、眼内炎及眼底肿瘤等。本综述通过分析不同给药途径在眼底疾病治疗中面临的挑战及障碍，对近年开展的相关研究中常见纳米药物递送系统的理化性质、在常见眼底疾病治疗研究的进展、优势、局限性及未来发展方向进行了总结。     

玻璃体切割术治疗眼内恶性肿瘤的热点与争议

视网膜母细胞瘤(RB)是婴幼儿最常见的原发性眼内恶性肿瘤,而脉络膜黑色素瘤是成人眼部最常见的原发性恶性肿瘤。随着眼内肿瘤诊断和治疗方法和技术的不断进步,患者的生存率显著提高,生存时间明显延长,眼内恶性肿瘤治疗目的也从单纯的挽救患者生命逐渐转变为在挽救生命的基础上尽量保全眼球。尽管目前眼内恶性肿瘤的治疗方案多样,但是对于部分难治性肿瘤,达到保全眼球的目标仍然具有很大挑战。近年来随着手术设备和操作技术的改进,玻璃体切割术再次成为难治性眼内期RB及脉络膜黑色素瘤的治疗方法之一,为这些眼内恶性肿瘤患者保全眼球带来了希望。然而,这种疗法仍有一定的并发症,因此存在争议,在治疗过程中一定要谨慎选择病例,小心实施手术,积极结合其他化学疗法和/或放射治疗及局部治疗方案,并且严密随访。